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Updated: Jul 5, 2025
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Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
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Drugging the entire human proteome: Are we there yet?
Micholas Dean Smith1, L Darryl Quarles2, Omar Demerdash3
1University of Tennessee/Oak Ridge National Laboratory Center for Molecular Biophysics, Oak Ridge, TN 37830, USA; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA.
Drug Discovery Today
|January 21, 2024
Summary
Proteome-wide virtual high-throughput screening (VHTS) using protein 3D structures is becoming feasible. Both physics-based docking and AI approaches show promise for drug discovery, with ongoing improvements expected.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Chemistry
Background:
- The human proteome comprises ~20,000 proteins, each a potential drug target.
- The availability of 3D protein structures is rapidly increasing.
- Drug discovery relies on identifying compounds that modulate protein function.
Purpose of the Study:
- To discuss the prospects of proteome-wide virtual high-throughput screening (VHTS).
- To compare physics-based docking and AI-driven VHTS methodologies.
- To assess the current and future potential of VHTS for drug discovery.
Main Methods:
- Review of physics-based (docking) VHTS approaches.
- Evaluation of AI-based VHTS methods.
- Analysis of large-scale compound databases applied to thousands of protein targets.
Main Results:
- Preliminary proteome-wide screens are achievable with current technologies.
- Both docking and AI VHTS are being applied to extensive target and compound libraries.
- Methodological advancements are crucial for enhancing VHTS accuracy.
Conclusions:
- Proteome-wide VHTS is a promising strategy for accelerating drug discovery.
- The integration of structural biology and computational methods is key.
- Continued development in VHTS algorithms will improve target identification and compound screening efficiency.
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